Cell adhesion and migration contribute to normal processes such as differentiation, embryonic development, and wound healing as well as to the progression of diseases and pathological conditions that can result from either acute or chronic exposure to environmental toxicants, such as cancer and inflammatory responses. Key mechanistic steps in these processes involve the interactions of extracellular glycoproteins--such as fibronectin, laminin, and collagens--with specific adhesive receptors, the best characterized of which are the integrins, a family of heterodimeric complexes consisting of an alpha subunit and a beta subunit. Integrins are highly regulated receptors that can exist in either an active or inactive state. The overall goal of our research is to characterize the molecular mechanisms of integrin-mediated adhesion processes, integrin activation, and the resulting downstream processes induced by adhesive proteins such as fibronectin important for the control of proliferation, adhesion, migration, and invasion of human tumor cell. Our current work focuses on biochemical and biological consequences of integrin activation, ligand occupancy, and the signal transduction pathways that play roles in the modulation of cell-cell and cell-substrate adhesion of tumor cells. The precise roles of these signaling processes in the mechanism of integrin function are currently being characterized.